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  3. Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis
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Research

Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g3009 (Published 13 May 2014) Cite this as: BMJ 2014;348:g3009
  1. Rik J B Loymans, general practitioner1,
  2. Armin Gemperli, assistant professor234,
  3. Judith Cohen, general practitioner1,
  4. Sidney M Rubinstein, senior researcher5,
  5. Peter J Sterk, professor6,
  6. Helen K Reddel, research leader7,
  7. Peter Jüni, professor2,
  8. Gerben ter Riet, associate professor1
  1. 1Department of General Practice, Academic Medical Center, University of Amsterdam, PO box 22700, 1105 DE, Amsterdam, Netherlands
  2. 2Division of Clinical Epidemiology and Biostatistics, Institute of Social and Preventive Medicine, University of Bern, Berne, Switzerland
  3. 3Department of Health Sciences and Health Policy, University of Lucerne, Lucerne, Switzerland
  4. 4Swiss Paraplegic Research, Nottwil, Switzerland
  5. 5Department of Health Sciences, Section Health Economics and Health Technology Assessment, VU University Amsterdam, Amsterdam, Netherlands
  6. 6Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
  7. 7Clinical Management Group, Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
  1. Correspondence to: R J B Loymans r.j.loijmans{at}amc.nl
  • Accepted 14 April 2014

Abstract

Objective To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma.

Design Systematic review and network meta-analysis using Bayesian statistics.

Data sources Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate.

Eligibility criteria Trials of adults with asthma randomised to maintenance treatments of at least 24 weeks duration and that reported on asthma exacerbations in full text. Low dose inhaled corticosteroid treatment was the comparator strategy. The primary effectiveness outcome was the rate of severe exacerbations. The secondary outcome was the composite of moderate or severe exacerbations. The rate of withdrawal was analysed as a safety outcome.

Results 64 trials with 59 622 patient years of follow-up comparing 15 strategies and placebo were included. For prevention of severe exacerbations, combined inhaled corticosteroids and long acting β agonists as maintenance and reliever treatment and combined inhaled corticosteroids and long acting β agonists in a fixed daily dose performed equally well and were ranked first for effectiveness. The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95% credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other combined strategies were not superior to inhaled corticosteroids and all single drug treatments were inferior to single low dose inhaled corticosteroids. Safety was best for conventional best (guideline based) practice and combined maintenance and reliever therapy.

Conclusions Strategies with combined inhaled corticosteroids and long acting β agonists are most effective and safe in preventing severe exacerbations of asthma, although some heterogeneity was observed in this network meta-analysis of full text reports.

Footnotes

  • We thank Faridi van Etten-Jamaludin, clinical librarian, and René Spijker, clinical librarian and trial search coordinator of the Dutch Cochrane Collaboration at the Academic Medical Center for their assistance with the search strategy; and Chris Cates, coordinating editor, and Elizabeth Stovold, trial search coordinator of the Cochrane Airways Group for making the Cochrane Airways Group Register of Trials accessible and conducting the searches.

  • This study was registered in the PROSPERO database as CRD4201200199 (www.crd.york.ac.uk/Prospero/).

  • Contributors: GtR and RJBL conceived the study. RJBL, GtR, SMR, HKR, JC, PJS, PJ, and AG contributed to the study protocol. RJBL and JC selected reports and extracted the data. RJBL, AG, GtR, and PJ analysed and interpreted the data. RJBL and GtR wrote the first draft of the manuscript. All authors critically revised the manuscript for intellectual content and approved the final version. They had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. RJBL and GtR act as guarantors.

  • Funding: This investigator initiated study was not supported by any industrial or public funding.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; HKR has participated on advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Novartis, is participating on a joint data monitoring committee for AstraZeneca, GlaxoSmithKline, Merck, and Novartis, has provided consultancy services for AstraZeneca, GlaxoSmithKline, and Mundipharma, has provided continuing medical education presentations at symposiums funded by AstraZeneca, Boehringer Ingelheim, Getz, GlaxoSmithKline, and Merck, and has received unconditional research funding from AstraZeneca and GlaxoSmithKline. PJ is an unpaid member of steering groups or executive committees of trials funded by Abbott Vascular, Biosensors, Medtronic, and St Jude Medical. CTU Bern, which is part of the University of Bern, has a staff policy of not accepting individual honorariums or consultancy fees. However, CTU Bern is involved in the design, conduct, or analysis of clinical studies funded by Abbott Vascular, Ablynx, Amgen, AstraZeneca, Biosensors, Biotronic, Boehrhinger Ingelheim, Eisai, Eli Lilly, Exelixis, Geron, Gilead Sciences, Nestlé, Novartis, Novo Nordisc, Padma, Roche, Schering-Plough, St Jude Medical, and Swiss Cardio Technologies; there are no non-financial interests that may be relevant to the submitted work.

  • Ethical approval: Not required.

  • Data sharing: Dataset and statistical code are available from the corresponding author at r.j.loijmans{at}amc.nl.

  • Transparency: The lead author (the manuscript’s guarantor), affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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